This study comprehensively investigates the changing biodistribution of fluorescent-labelled polystyrene latex bead nanoparticles in a mouse model of inflammation. Since inflammation alters systemic ...circulatory properties, increases vessel permeability and modulates the immune system, we theorised that systemic inflammation would alter nanoparticle distribution within the body. This has implications for prospective nanocarrier-based therapies targeting inflammatory diseases. Low dose lipopolysaccharide (LPS), a bacterial endotoxin, was used to induce an inflammatory response, and 20 nm, 100 nm or 500 nm polystyrene nanoparticles were administered after 16 hours. HPLC analysis was used to accurately quantify nanoparticle retention by each vital organ, and tissue sections revealed the precise locations of nanoparticle deposition within key tissues. During inflammation, nanoparticles of all sizes redistributed, particularly to the marginal zones of the spleen. We found that LPS-induced inflammation induces splenic macrophage polarisation and alters leukocyte uptake of nanoparticles, with size-dependent effects. In addition, spleen vasculature becomes significantly more permeable following LPS treatment. We conclude that systemic inflammation affects nanoparticle distribution by multiple mechanisms, in a size dependent manner.
Summary
Background
GIDEON (Global Investigation of therapeutic DEcisions in hepatocellular carcinoma HCC and Of its treatment with sorafeNib) is a global, prospective, non‐interventional study ...undertaken to evaluate the safety of sorafenib in patients with unresectable HCC in real‐life practice, including Child‐Pugh B patients who were excluded from clinical trials.
Methods
Patients with unresectable HCC, for whom the decision to treat with sorafenib, based on the approved label and prescribing guidelines, had been taken by their physician, were eligible for inclusion. Demographic data and disease/medical history were recorded at entry. Sorafenib dosing and adverse events (AEs) were collected at follow‐up visits. The second interim analysis was undertaken when ~1500 treated patients were followed up for ≥ 4 months.
Results
Of the 1571 patients evaluable for safety, 61% had Child‐Pugh A status and 23% Child‐Pugh B. The majority of patients (74%) received the approved 800 mg initial sorafenib dose, regardless of Child‐Pugh status; however, median duration of therapy was shorter in Child‐Pugh B patients. The majority of drug‐related AEs were grade 1 or 2, and the most commonly reported were consistent with previous reports. The incidence and nature of drug‐related AEs were broadly similar across Child‐Pugh, Barcelona Clinic Liver Cancer (BCLC) and initial dosing subgroups, and consistent with the overall population.
Conclusions
Consistent with the first interim analysis, overall safety profile and dosing strategy are similar across Child‐Pugh subgroups. Safety findings also appear comparable irrespective of initial sorafenib dose or BCLC stage. Final analyses in > 3000 patients are ongoing.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
We theoretically and numerically analyze thermal invisibility based on the concept of scattering cancellation and mantle cloaking. We show that a small object can be made completely invisible to heat ...diffusion waves, by tailoring the heat conductivity of the spherical shell enclosing the object. This means that the thermal scattering from the object is suppressed, and the heat flow outside the object and the cloak made of these spherical shells behaves as if the object is not present. Thermal invisibility may open new vistas in hiding hot spots in infrared thermography, military furtivity, and electronics heating reduction.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
We present the second data release (DR2) of the X-shooter Spectral Library (XSL), which contains all the spectra obtained over the six semesters of that program. This release supersedes our first ...data release from Chen et al. (2014, A&A, 565, A117), with a larger number of spectra (813 observations of 666 stars) and with a more extended wavelength coverage as the data from the near-infrared arm of the X-shooter spectrograph are now included. The DR2 spectra then consist of three segments that were observed simultaneously and, if combined, cover the range between ∼300 nm and ∼2.45
μ
m at a spectral resolving power close to
R
= 10 000. The spectra were corrected for instrument transmission and telluric absorption, and they were also corrected for wavelength-dependent flux-losses in 85% of the cases. On average, synthesized broad-band colors agree with those of the MILES library and of the combined IRTF and Extended IRTF libraries to within ∼1%. The scatter in these comparisons indicates typical errors on individual colors in the XSL of 2−4%. The comparison with 2MASS point source photometry shows systematics of up to 5% in some colors, which we attribute mostly to zero-point or transmission curve errors and a scatter that is consistent with the above uncertainty estimates. The final spectra were corrected for radial velocity and are provided in the rest-frame (with wavelengths in air). The spectra cover a large range of spectral types and chemical compositions (with an emphasis on the red giant branch), which makes this library an asset when creating stellar population synthesis models or for the validation of near-ultraviolet to near-infrared theoretical stellar spectra across the Hertzsprung-Russell diagram.
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FMFMET, NUK, UL, UM, UPUK
Inspired by the remarkable ability of natural protein switches to sense and respond to a wide range of environmental queues, here we report a strategy to engineer synthetic protein switches by using ...DNA strand displacement to dynamically organize proteins with highly diverse and complex logic gate architectures. We show that DNA strand displacement can be used to dynamically control the spatial proximity and the corresponding fluorescence resonance energy transfer between two fluorescent proteins. Performing Boolean logic operations enabled the explicit control of protein proximity using multi-input, reversible and amplification architectures. We further demonstrate the power of this technology beyond sensing by achieving dynamic control of an enzyme cascade. Finally, we establish the utility of the approach as a synthetic computing platform that drives the dynamic reconstitution of a split enzyme for targeted prodrug activation based on the sensing of cancer-specific miRNAs.
Aeromonas dhakensis, often phenotypically identified as Aeromonas hydrophila, is an important human pathogen. The present study aimed to compare the clinical and biological features of A. dhakensis ...and A. hydrophila isolates from human wounds. A total of 80 Aeromonas wound isolates collected between January 2004 and April 2011 were analysed. The species was identified by the DNA sequence matching of rpoD and gyrB (or rpoB if necessary). Most of the Aeromonas isolates were identified as A. dhakensis (37, 46.3%), and 13 (16.3%) as A. hydrophila. Both species alone can cause severe skin and soft-tissue infections. More A. dhakensis isolates were found in wounds exposed to environmental water (32.4% vs 0%, p 0.042). More biofilm formation was noted among A. dhakensis isolates (mean optical density at 570 nm, 1.23 ± 0.09 vs 0.78 ± 0.21, p 0.03). The MICs of ceftriaxone, imipenem and gentamicin for A. dhakensis isolates were higher (p <0.0001, <0.04, and <0.01, respectively). The survival rates of Caenorhabditis elegans co-incubated with A. dhakensis from day 1 to day 3 were lower than those of worms infected with A. hydrophila in liquid toxicity assays (all p values <0.01). Isolates of A. dhakensis exhibited more cytotoxicity, as measured by the released leucocyte lactate dehydrogenase levels in human normal skin fibroblast cell lines (29.6 ± 1.2% vs 20.6 ± 0.6%, p <0.0001). The cytotoxin gene ast was primarily present in A. hydrophila isolates (100% vs 2.7%, p <0.0001). In summary, A. dhakensis is the predominant species among Aeromonas wound isolates, and more virulent than A. hydrophila.
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BFBNIB, DOBA, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, UILJ, UKNU, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Collagen hydrolysate can stabilize Zn and Li electrodeposition in metal ion batteries.
Lithium (Li) or zinc (Zn) metal anodes have attracted interest for battery research due to their high ...theoretical capacities and low redox potentials. However, uncontrollable dendrite growth, especially under high current (>4 mA cm
−2
), precludes reversable cycling in Li or Zn metal batteries with a high-loading (>4 mAh cm
−2
), precludes reversable cycling in Li or Zn metal batteries with high-loading (>4 mAh cm
−2
) cathode. We report a cation regulation mechanism to address this failure. Collagen hydrolysate coated on absorbed glass mat (CH@AGM) can simultaneously induce a deionization shock inside the separator and spread cations on the anode to promote uniform electrodeposition. Employing 24 mAh cm
−2
cathodes, Li and Zn metal batteries with CH@AGM delivered 600 cycles with a Coulombic efficiency of 99.7%. In comparison, pristine Li and Zn metal batteries only survive for 10 and 100 cycles, respectively. This approach enabled 400 cycles in a 200 Ah-class Zn metal battery, which suggests a scalable method to achieve dendrite-free anodes in various batteries.
Using electrical detection of a strongly coupled spin-photon system comprised of a microwave cavity mode and two magnetic samples, we demonstrate the long distance manipulation of spin currents. This ...distant control is not limited by the spin diffusion length, instead depending on the interplay between the local and global properties of the coupled system, enabling systematic spin current control over large distance scales (several centimeters in this work). This flexibility opens the door to improved spin current generation and manipulation for cavity spintronic devices.
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CMK, CTK, FMFMET, IJS, NUK, PNG, UM
Defect modes in two-dimensional periodic photonic structures have found use in diverse optical devices. For example, photonic crystal cavities confine optical modes to subwavelength volumes and can ...be used for enhancement of nonlinearity, lasing and cavity quantum electrodynamics. Defect-core photonic crystal fibres allow for supercontinuum generation and endlessly single-mode fibres with large cores. However, these modes are notoriously fragile: small structural change leads to significant detuning of resonance frequency and mode volume. Here, we show that photonic topological crystalline insulator structures can be used to topologically protect the mode frequency at mid-gap and minimize the volume of a photonic defect mode. We experimentally demonstrate this in a femtosecond-laser-written waveguide array by observing the presence of a topological zero mode confined to the corner of the array. The robustness of this mode is guaranteed by a topological invariant that protects zero-dimensional states embedded in a two-dimensional environment—a novel form of topological protection that has not been previously demonstrated.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, SBMB, UL, UM, UPUK
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